Low dose oral administration of cytokines for treatment of allergic asthma

Abstract

Many inflammatory diseases are characterized by an imbalance among lymphocyte populations, in particular Th1, Th2 and the recently described Th17 cells. The Th1/Th2 imbalance is linked to many factors, but certainly the role of cytokines is essential.In Th2 diseases IL-4 expression is predominant, while Th1 pathologies are characterized by high expression of IFN-γ and IL-12. Though today the therapeutical proposal for many inflammatory diseases aims to re-establish normal levels of Th1/Th2 cytokines, the pharmacological use of cytokines, which are very active molecules, is limited by the possible collateral effects. Therefore, our study aims to determine, in a murine model of allergic asthma, the possible therapeutic activity of low dose cytokines solutions, mechanically activated. We found that oral administration of low doses IL-12 plus IFN-γ is able to solve the bronchial hyperresponsiveness condition of mice, establishing normal cytokine levels. The anti-asthma activity was confirmed by histological analysis of lungs and bronchoalveolar lavage fluid cell count. Serum ovalbumin-specific IgE was also significantly inhibited by treatment with low-dose activated cytokines solution. These findings may suggest a novel approach to diseases which involve a Th1/Th2 imbalance.

Low Dose of IL-12 Stimulates T Cell Response in Cultures of PBMCs Derived from Non Small Cell Lung Cancer Patients

“…Since IL-12 is an important modulator of immune response and mediates various anti-tumor effects, we analyzed the ability of low doses of IL-12 to modulate CD4 subpopulation in cultures of PBMC derived from lung cancer patients. In literature evidences of efficacy of low doses of IL-12 on modulation of Th1 vs Th2 has been demonstrated in an asthma pre-clinical model [20], suggesting the possibility to utilize low doses of IL-12 to act on other immune pathologies characterized by Th1/Th2 imbalance.…”

“…In this study Gariboldi et al tested different doses of IL-12 for the treatment of asthma in mice and identified 0.01 pg/ml as the lowest and more effecttive dose [20].…”

“…Recently, evidences of efficacy of low doses of IL-12 on modulation of Th1 vs Th2 has been demonstrated in an asthma pre-clinical model [20], suggesting a novel therapeutic approach to diseases which involve a Th1/ Th2 imbalance. In this study Gariboldi et al tested different doses of IL-12 for the treatment of asthma in mice and identified 0.01 pg/ml as the lowest and more effecttive dose [20].…”

Skin as a Psychoneuroendocrine Immunology Microcosm: The New Frontier of Low Dose Therapy With Cytokines and Growth Factors in the Systemic Treatment of Chronic Autoimmune Inflammatory Diseases in Dermatology

“…A possible answer can be found in the LDM approach. The availability of low dose SKA signaling molecules (cytokines, growth factors, hormones, and neuropeptides) makes it possible to use lower doses of activated molecules (active range between picomoles and femtomeoles) (18)(19)(20)(21)(22) with therapeutic outcomes comparable to those induced by high doses but without the side effects.…”

Immunomodulation by Stemona tuberosa ethanol extract in vitro and in ovalbumin-induced mouse asthma model

“…The levels of these cytokine result in the imbalance between Th1 and 2 responses. A greater abundant presence of Th2 cells and their relative cytokines and a decrease of Th1 cells and their relative cytokines are markers of the presence of the disease, thus, a way to cure asthma focuses on modulating the levels of these cytokines (Gariboldi et al, 2009). Although regulation of the Th1/Th2 imbalance remains unclear, and the differentiation of T-helper cells is sophisticatedly controlled, growing evidence suggests that T-bet and GATA-3 (GATA-binding protein 3) are 2 major T-helper-specific transcription factors that play a key role in Th cells differentiation (Yu et al, 2003).…”